Identifying and treating metabolic deficiencies in patients with treatment-resistant depression can improve symptoms and even lead to remission, according to new research from the University of Pittsburgh School of Medicine.

Major depressive disorder, also referred to simply as depression, affects 3 in 100 people, according to Mind, with depression being the majority cause of suicides.

Unfortunately, at least 15% of patients don’t find relief from conventional treatments such as antidepressant medications and psychotherapy, explained lead study investigator Lisa Pan, MD professor of psychiatry, clinical and translational science, Pitt School of Medicine.

The original case

Five years ago Dr Pan and David Brent, MD Endowed Chair in suicide studies at Pitt, treated a teen with a history of suicide attempts and long-standing depression.

“Over a period of years, we tried every treatment available to help this patient, and yet he still found no relief from his depression symptoms,” she explained.

Finding deficiencies

Searching for answers through a series of biochemical tests, the scientists discovered that the patient had a cerebrospinal fluid deficiency in biopterin, a protein involved in the synthesis of several brain signalling chemicals called neurotransmitters.

After receiving an analogue of biopterin to correct the deficiency, the patient’s depression symptoms largely disappeared and today he is a thriving college student.

The success prompted the researchers to examine other young adults with depression who were not responding to treatment.

Beginning clinical trials

In the trial, the researchers looked for metabolic abnormalities in 33 adolescents and young adults with treatment-resistant depression and 16 controls. Although the specific metabolites affected differed among patients, the researchers found that 64% of the patients had a deficiency in neurotransmitter metabolism, compared with none of the controls.

Continued improvement

In almost all patients, treating the underlying deficiency improved their depression symptoms, with some experiencing complete remission. “The further along the patients’ progress in the treatment, the better they are getting”, Dr Pan added.

“It’s really exciting that we now have another avenue to pursue for patients for whom our currently available treatments have failed, and is a potentially transformative finding for people with depression,” said Dr Pan.

“These findings indicate that there may be physiological mechanisms underlying depression that we can use to improve the quality of life in patients with this disabling illness,” said David Lewis, MD Thomas Detre Professor and Chair of Pitt’s Department of Psychiatry.